Multi-trait association analysis reveals shared genetic loci between Alzheimer’s disease and cardiovascular traits
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Several cardiovascular traits and diseases co-occur with Alzheimer’s disease. We mapped their shared genetic architecture using multi-trait genome-wide association studies. Subsequent fine-mapping and colocalisation highlighted 16 genetic loci associated with both Alzheimer’s and cardiovascular diseases. We prioritised rs11786896, which colocalised with Alzheimer’s disease, atrial fibrillation and expression of PLEC in the heart left ventricle, and rs7529220, which colocalised with Alzheimer’s disease, atrial fibrillation and expression of C1Q family genes. Single-cell RNA-sequencing data, co-expression network and protein-protein interaction analyses provided evidence for different mechanisms of PLEC, which is upregulated in left ventricular endothelium and cardiomyocytes with heart failure and in brain astrocytes with Alzheimer’s disease. Similar common mechanisms are implicated for C1Q in heart macrophages with heart failure and in brain microglia with Alzheimer’s disease. These findings highlight inflammatory and pleomorphic risk determinants for the co-occurrence of Alzheimer’s and cardiovascular diseases and suggest PLEC, C1Q and their interacting proteins as potential therapeutic targets.
Date Issued
2024-11-13
Date Acceptance
2024-10-14
Citation
Nature Communications, 2024, 15
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
15
Copyright Statement
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.nature.com/articles/s41467-024-53452-6
Publication Status
Published
Article Number
9827
Date Publish Online
2024-11-13